Simplified procedure for fractionation and structural characterisation of complex mixtures of N-linked glycans, released from HIV-1 gp120 and other highly glycosylated viral proteins

J Virol Methods. 1998 Dec;76(1-2):87-100. doi: 10.1016/s0166-0934(98)00127-x.

Abstract

HIV-1 gp120 is heavily glycosylated containing 24 N-glycosylation sites, and this makes elucidation of the significance of glycans at individual glycosylation sites a difficult task. A procedure is described where a complex mixture of biologically radiolabelled glycans of gp120, derived from a relatively small number of virus-infected cells may be characterized by a combination of N-glycanase release, single lectin separation, and normal phase HPLC (NP-HPLC). The method was applied in analysis of three N-linked glycosylation sites essential for the in vivo priming of T-cells, specific for an epitope in their vicinity (Sjölander, S., Bolmstedt, A., Akerblom, 1996. Virology 215, 124-133.). The carbohydrate compositions of wild type gp120 and of mutant variants gp120 lacking one, two, or all of these three active N-linked glycans were analysed. Cells were infected with r-vaccinia virus expressing wild-type gp120 or mutated gp120, or were infected with HIV-1BRU (wild type) or mutant virus variants. HIV-1 glycoproteins were purified by immunosorbent affinity chromatography and released glycans were separated on lectins, then analysed with NP-HPLC. Our data showed that the structural composition of glycans occupying two of the three glycosylation sites was heterogeneous but the site located adjacent to the T-cell epitope was equipped with one large, high mannose-type structure (> 11 units) with the capacity to cover a substantial part of the gp120 surface.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrate Conformation
  • Cell Line
  • Chromatography, Affinity
  • Chromatography, High Pressure Liquid
  • Electrophoresis, Polyacrylamide Gel
  • Epitopes
  • Glycosylation
  • HIV Envelope Protein gp120 / chemistry*
  • HIV Envelope Protein gp120 / metabolism
  • HIV-1 / chemistry*
  • HIV-1 / genetics
  • HIV-1 / physiology
  • Humans
  • Lectins / metabolism
  • Polysaccharides / chemistry*
  • Polysaccharides / isolation & purification*
  • Polysaccharides / metabolism
  • Precipitin Tests
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • T-Lymphocytes
  • Vaccinia virus / genetics
  • Viral Proteins / chemistry*
  • Viral Proteins / metabolism

Substances

  • Epitopes
  • HIV Envelope Protein gp120
  • Lectins
  • Polysaccharides
  • Recombinant Proteins
  • Viral Proteins